CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC)

CLARITY-Gastric 01

Patient / Population Intervention / Exposition Vergleich Endpunkt

In previously treated advanced CLDN18.2-positive gastroesophageal carcinoma, sonesitatug vedotin improved overall survival compared with investigator's choice of chemotherapy-based therapy.

N

532Patienten

Design

Randomised, open-label, global phase 3 trial in participants with unresectable locally advanced or metastatic CLDN18.2-positive (≥25% of tumour cells) gastroesophageal carcinoma after ≥1 prior therapy, first randomised 1:1:1 to one of two sonesitatug vedotin doses or investigator's choice of therapy, then randomised 1:1 to sonesitatug vedotin or investigator's choice once a dose was selected, stratified by region, prior gastrectomy and line of therapy (NCT06346392).

Endpunkt

Dual primary endpoints: overall survival in the 3L+ population and progression-free survival by BICR in the intent-to-treat (2L+) population. Key secondary endpoint: overall survival in the intent-to-treat population.

ErgebnisMedian OS in 3L+ was 10.0 vs 5.0 months with sonesitatug vedotin vs investigator's choice (HR 0.47, 95% CI 0.36-0.62; P<0.001). Median PFS by BICR in the ITT population was 4.2 vs 3.8 months (HR 0.77, 95% CI 0.62-0.96; P = 0.05), which did not meet the threshold for statistical significance. Median OS in the ITT population was 10.6 vs 6.4 months (HR 0.58, 95% CI 0.47-0.73; P<0.001), with HR 0.59 (95% CI 0.45-0.78) for CLDN18.2 ≥75% and HR 0.63 (95% CI 0.42-0.94) for ≥25-<75%. Grade ≥3 treatment-related adverse events occurred in 36.4% vs 44.8%, with grade ≥3 gastrointestinal toxicity in 11.1% vs 6.3%. Treatment-related adverse events led to death in 1.1% vs 0.8%.

Xu R, Janjigian YY, Chen M, et al. Presented at ESMO Congress 2026, abstract LBA7, 25 October. Not yet published.

Diskussion & Kritik

The trial met its 3L+ overall survival primary endpoint and its key secondary endpoint of overall survival in the ITT population, with large hazard ratios on a hard endpoint. The other primary endpoint, progression-free survival by BICR, was not significant, and with a median follow-up of 8.6 months the survival data are still early. The design was open label and the comparator was an investigator's choice of several regimens that differed by line and region. The abstract reports 532 of the 594 randomised participants, does not give results for the lower dose arm and does not break down efficacy by individual comparator regimen.